Table 1.

Acute ecstasy/MDMA and cortisol: neuroendocrine aspects of bioenergetic stress in recreational ecstasy users

MDMA in sedentary users	MDMA in the laboratory increases cortisol release. This increases metabolic activation and may en- hance the mood effects of the increased serotonin and dopamine released by MDMA.
Dancing in nondrug users	Physical activity and exertion can stimulate mild HPA axis activation and cortisol release. Feedback loops signal tiredness and rest breaks are taken. Hence normal dancing is essentially non-stressful. Strenuous dancing may comprise a mild metabolic stressor. Prolonged exertion (e.g. marathon run- ning) can be a strong metabolic stressor.
MDMA in active dancers	MDMA induces cortisol release and hence pro- vides the energy reserves for prolonged dancing. Dancing then increases this HPA activation fur- ther - leading to continued cortisol release. Stimu- lant drug plus physical activation may therefore have synergistic effects. The combination can in- duce intense sympathomimetic activation, strong serotonin-dopamine release and powerful mood activation.
MDMA in prolonged dancers	Continued dancing with further MDMA self-dosing will prolong the ‘desired’ clubbing experience. However this will be achieved at the expense of yet further acute metabolic stress. Potential dangers include metabolic overstimulation, physical ex- haustion and overheating. Neural overactivity and/or neurotoxicity may be exacerbated. Psycho- biological recovery problems will also be stron- ger.
Other environ- mental co-stimulants	Potential factors include loud and prolonged mu- sic, dynamic light shows, closely packed crowds, psychosocial and sexual stimulation, and thermal stress. Some users may seek out hot thermal envi- ronments to maintain the acute drug experience.
Stimulant co-drugs	Other central nervous system stimulants such as amphetamine or cocaine may add to further corti- sol release, and so heighten acute bioenergetic stress through synergistic neurohormonal-neu- rotransmitter activation.